KR20070120190A

KR20070120190A - 아밀로이드 억제 화합물의 제약 제제

아밀로이드 억제 화합물의 제약 제제 Download PDF

Info

Publication number: KR20070120190A
Authority: KR; South Korea
Prior art keywords: active agent; average; disease; dose; alzheimer
Prior art date: 2005-04-12
Legal status : Withdrawn

Application number

KR1020077026152A

Other languages

English (en)

Korean (ko)

Inventor

줄리 라우린

데니스 가르차우

Original Assignee

뉴로켐 (인터내셔널) 리미티드

Priority date

2005-04-12

Filing date

2006-04-12

Publication date

2007-12-21

2006-04-12 Application filed by 뉴로켐 (인터내셔널) 리미티드 filed Critical 뉴로켐 (인터내셔널) 리미티드

2007-12-21 Publication of KR20070120190A publication Critical patent/KR20070120190A/ko

Status Withdrawn legal-status Critical Current

Links

230000002401 inhibitory effect Effects 0.000 title abstract description 64
150000001875 compounds Chemical class 0.000 title description 312
239000008194 pharmaceutical composition Substances 0.000 title description 62
238000000034 method Methods 0.000 claims abstract description 169
239000003814 drug Substances 0.000 claims abstract description 150
229940124597 therapeutic agent Drugs 0.000 claims abstract description 94
239000003795 chemical substances by application Substances 0.000 claims abstract description 74
230000001225 therapeutic effect Effects 0.000 claims description 287
239000000203 mixture Substances 0.000 claims description 251
238000009472 formulation Methods 0.000 claims description 201
208000024827 Alzheimer disease Diseases 0.000 claims description 148
239000013543 active substance Substances 0.000 claims description 138
SNKZJIOFVMKAOJ-UHFFFAOYSA-N 3-Amino-1-propanesulfonic acid Natural products NCCCS(O)(=O)=O SNKZJIOFVMKAOJ-UHFFFAOYSA-N 0.000 claims description 106
230000002496 gastric effect Effects 0.000 claims description 104
208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 102
210000004556 brain Anatomy 0.000 claims description 73
150000003839 salts Chemical class 0.000 claims description 68
230000036470 plasma concentration Effects 0.000 claims description 61
LZXHHNKULPHARO-UHFFFAOYSA-M (3,4-dichlorophenyl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].C1=C(Cl)C(Cl)=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 LZXHHNKULPHARO-UHFFFAOYSA-M 0.000 claims description 60
238000011282 treatment Methods 0.000 claims description 55
230000003920 cognitive function Effects 0.000 claims description 34
238000012360 testing method Methods 0.000 claims description 28
230000001965 increasing effect Effects 0.000 claims description 27
210000001175 cerebrospinal fluid Anatomy 0.000 claims description 25
206010012289 Dementia Diseases 0.000 claims description 23
230000000694 effects Effects 0.000 claims description 23
230000007423 decrease Effects 0.000 claims description 21
230000006872 improvement Effects 0.000 claims description 20
230000002265 prevention Effects 0.000 claims description 19
230000009467 reduction Effects 0.000 claims description 18
238000002360 preparation method Methods 0.000 claims description 17
230000003111 delayed effect Effects 0.000 claims description 14
239000002552 dosage form Substances 0.000 claims description 13
230000002490 cerebral effect Effects 0.000 claims description 10
206010003694 Atrophy Diseases 0.000 claims description 9
230000037444 atrophy Effects 0.000 claims description 9
238000013270 controlled release Methods 0.000 claims description 8
230000003204 osmotic effect Effects 0.000 claims description 8
230000002035 prolonged effect Effects 0.000 claims description 8
239000000090 biomarker Substances 0.000 claims description 7
230000000087 stabilizing effect Effects 0.000 claims description 7
238000013268 sustained release Methods 0.000 claims description 7
206010059245 Angiopathy Diseases 0.000 claims description 6
230000001054 cortical effect Effects 0.000 claims description 6
210000001320 hippocampus Anatomy 0.000 claims description 6
239000012730 sustained-release form Substances 0.000 claims description 6
102000044159 Ubiquitin Human genes 0.000 claims description 4
108090000848 Ubiquitin Proteins 0.000 claims description 4
230000001149 cognitive effect Effects 0.000 claims description 4
230000003247 decreasing effect Effects 0.000 claims description 4
230000001991 pathophysiological effect Effects 0.000 claims description 4
229940122041 Cholinesterase inhibitor Drugs 0.000 claims description 2
229940099433 NMDA receptor antagonist Drugs 0.000 claims description 2
239000000544 cholinesterase inhibitor Substances 0.000 claims description 2
239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 claims description 2
238000011321 prophylaxis Methods 0.000 claims 3
230000003941 amyloidogenesis Effects 0.000 abstract description 127
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 125
201000010099 disease Diseases 0.000 abstract description 122
206010002022 amyloidosis Diseases 0.000 abstract description 99
239000003826 tablet Substances 0.000 description 71
125000000217 alkyl group Chemical group 0.000 description 63
-1 phosphorylated-tau Proteins 0.000 description 60
238000013103 analytical ultracentrifugation Methods 0.000 description 59
229910052739 hydrogen Inorganic materials 0.000 description 54
239000001257 hydrogen Substances 0.000 description 54
125000003118 aryl group Chemical group 0.000 description 52
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 49
150000002431 hydrogen Chemical group 0.000 description 44
102000013455 Amyloid beta-Peptides Human genes 0.000 description 42
108010090849 Amyloid beta-Peptides Proteins 0.000 description 42
102000009091 Amyloidogenic Proteins Human genes 0.000 description 42
108010048112 Amyloidogenic Proteins Proteins 0.000 description 42
229940079593 drug Drugs 0.000 description 41
108090000765 processed proteins & peptides Proteins 0.000 description 40
238000000576 coating method Methods 0.000 description 39
238000000151 deposition Methods 0.000 description 39
150000002148 esters Chemical class 0.000 description 37
210000004027 cell Anatomy 0.000 description 36
239000003981 vehicle Substances 0.000 description 36
239000002253 acid Substances 0.000 description 35
230000008021 deposition Effects 0.000 description 35
125000000753 cycloalkyl group Chemical group 0.000 description 31
125000003342 alkenyl group Chemical group 0.000 description 30
229910052757 nitrogen Inorganic materials 0.000 description 30
108090000623 proteins and genes Proteins 0.000 description 29
125000000304 alkynyl group Chemical group 0.000 description 28
239000011248 coating agent Substances 0.000 description 27
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 27
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 27
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 27
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 27
102000004196 processed proteins & peptides Human genes 0.000 description 27
102000004169 proteins and genes Human genes 0.000 description 26
229920002683 Glycosaminoglycan Polymers 0.000 description 25
102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 25
108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 25
125000000623 heterocyclic group Chemical group 0.000 description 25
230000035772 mutation Effects 0.000 description 25
235000018102 proteins Nutrition 0.000 description 25
108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 23
239000002702 enteric coating Substances 0.000 description 23
238000009505 enteric coating Methods 0.000 description 23
230000006870 function Effects 0.000 description 23
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 23
208000037259 Amyloid Plaque Diseases 0.000 description 22
239000004480 active ingredient Substances 0.000 description 22
229910052760 oxygen Inorganic materials 0.000 description 22
125000005358 mercaptoalkyl group Chemical group 0.000 description 21
150000007513 acids Chemical class 0.000 description 20
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 20
125000002883 imidazolyl group Chemical group 0.000 description 20
239000000463 material Substances 0.000 description 20
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 19
239000001301 oxygen Substances 0.000 description 19
125000001425 triazolyl group Chemical group 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
125000004432 carbon atom Chemical group C* 0.000 description 18
239000012634 fragment Substances 0.000 description 18
125000000335 thiazolyl group Chemical group 0.000 description 18
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 17
229920000642 polymer Polymers 0.000 description 17
208000024891 symptom Diseases 0.000 description 17
239000011324 bead Substances 0.000 description 16
239000002775 capsule Substances 0.000 description 16
229920002472 Starch Polymers 0.000 description 15
108010064397 amyloid beta-protein (1-40) Proteins 0.000 description 15
230000003942 amyloidogenic effect Effects 0.000 description 15
230000015572 biosynthetic process Effects 0.000 description 15
150000001768 cations Chemical class 0.000 description 15
238000000338 in vitro Methods 0.000 description 15
239000004615 ingredient Substances 0.000 description 15
230000003993 interaction Effects 0.000 description 15
239000010410 layer Substances 0.000 description 15
235000019698 starch Nutrition 0.000 description 15
208000001072 type 2 diabetes mellitus Diseases 0.000 description 15
150000001413 amino acids Chemical group 0.000 description 14
239000002585 base Substances 0.000 description 14
230000008859 change Effects 0.000 description 14
208000010877 cognitive disease Diseases 0.000 description 14
239000008107 starch Substances 0.000 description 14
229940032147 starch Drugs 0.000 description 14
125000001424 substituent group Chemical group 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
230000006933 amyloid-beta aggregation Effects 0.000 description 13
229910052736 halogen Inorganic materials 0.000 description 13
150000002367 halogens Chemical class 0.000 description 13
239000003607 modifier Substances 0.000 description 13
201000010374 Down Syndrome Diseases 0.000 description 12
238000009825 accumulation Methods 0.000 description 12
210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 12
230000002354 daily effect Effects 0.000 description 12
239000003085 diluting agent Substances 0.000 description 12
238000004090 dissolution Methods 0.000 description 12
238000005755 formation reaction Methods 0.000 description 12
208000023769 AA amyloidosis Diseases 0.000 description 11
102000019034 Chemokines Human genes 0.000 description 11
108010012236 Chemokines Proteins 0.000 description 11
229920000168 Microcrystalline cellulose Polymers 0.000 description 11
206010035226 Plasma cell myeloma Diseases 0.000 description 11
102000016611 Proteoglycans Human genes 0.000 description 11
108010067787 Proteoglycans Proteins 0.000 description 11
125000004453 alkoxycarbonyl group Chemical group 0.000 description 11
125000004448 alkyl carbonyl group Chemical group 0.000 description 11
229940024606 amino acid Drugs 0.000 description 11
235000001014 amino acid Nutrition 0.000 description 11
125000000539 amino acid group Chemical group 0.000 description 11
229910052799 carbon Inorganic materials 0.000 description 11
239000007884 disintegrant Substances 0.000 description 11
235000019813 microcrystalline cellulose Nutrition 0.000 description 11
229940016286 microcrystalline cellulose Drugs 0.000 description 11
239000008108 microcrystalline cellulose Substances 0.000 description 11
230000004770 neurodegeneration Effects 0.000 description 11
210000000056 organ Anatomy 0.000 description 11
239000008188 pellet Substances 0.000 description 11
239000000843 powder Substances 0.000 description 11
210000002784 stomach Anatomy 0.000 description 11
125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 11
125000003831 tetrazolyl group Chemical group 0.000 description 11
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 10
235000021355 Stearic acid Nutrition 0.000 description 10
125000002091 cationic group Chemical group 0.000 description 10
230000003013 cytotoxicity Effects 0.000 description 10
231100000135 cytotoxicity Toxicity 0.000 description 10
235000019441 ethanol Nutrition 0.000 description 10
230000002068 genetic effect Effects 0.000 description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 description 10
239000012528 membrane Substances 0.000 description 10
210000004379 membrane Anatomy 0.000 description 10
208000027061 mild cognitive impairment Diseases 0.000 description 10
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 10
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 10
208000033808 peripheral neuropathy Diseases 0.000 description 10
239000008117 stearic acid Substances 0.000 description 10
210000001519 tissue Anatomy 0.000 description 10
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 9
102000008055 Heparan Sulfate Proteoglycans Human genes 0.000 description 9
229920002971 Heparan sulfate Polymers 0.000 description 9
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
108090000054 Syndecan-2 Proteins 0.000 description 9
125000001931 aliphatic group Chemical group 0.000 description 9
125000003545 alkoxy group Chemical group 0.000 description 9
125000003277 amino group Chemical group 0.000 description 9
125000003710 aryl alkyl group Chemical group 0.000 description 9
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 9
125000004122 cyclic group Chemical group 0.000 description 9
235000019700 dicalcium phosphate Nutrition 0.000 description 9
229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 9
229940125396 insulin Drugs 0.000 description 9
238000004519 manufacturing process Methods 0.000 description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
239000000758 substrate Substances 0.000 description 9
229910052717 sulfur Inorganic materials 0.000 description 9
238000002560 therapeutic procedure Methods 0.000 description 9
102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 8
229920003134 Eudragit® polymer Polymers 0.000 description 8
208000034846 Familial Amyloid Neuropathies Diseases 0.000 description 8
206010019889 Hereditary neuropathic amyloidosis Diseases 0.000 description 8
102000004877 Insulin Human genes 0.000 description 8
108090001061 Insulin Proteins 0.000 description 8
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 8
229930006000 Sucrose Natural products 0.000 description 8
208000036142 Viral infection Diseases 0.000 description 8
125000005129 aryl carbonyl group Chemical group 0.000 description 8
239000000872 buffer Substances 0.000 description 8
206010012601 diabetes mellitus Diseases 0.000 description 8
239000002662 enteric coated tablet Substances 0.000 description 8
125000001072 heteroaryl group Chemical group 0.000 description 8
125000005842 heteroatom Chemical group 0.000 description 8
208000002780 macular degeneration Diseases 0.000 description 8
235000019359 magnesium stearate Nutrition 0.000 description 8
229920001223 polyethylene glycol Polymers 0.000 description 8
239000000243 solution Substances 0.000 description 8
239000005720 sucrose Substances 0.000 description 8
235000000346 sugar Nutrition 0.000 description 8
201000007905 transthyretin amyloidosis Diseases 0.000 description 8
230000002792 vascular Effects 0.000 description 8
230000009385 viral infection Effects 0.000 description 8
208000023761 AL amyloidosis Diseases 0.000 description 7
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 7
102000001049 Amyloid Human genes 0.000 description 7
108010094108 Amyloid Proteins 0.000 description 7
108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 7
101710137189 Amyloid-beta A4 protein Proteins 0.000 description 7
101710151993 Amyloid-beta precursor protein Proteins 0.000 description 7
102100022704 Amyloid-beta precursor protein Human genes 0.000 description 7
208000005531 Immunoglobulin Light-chain Amyloidosis Diseases 0.000 description 7
206010061218 Inflammation Diseases 0.000 description 7
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 7
108010071690 Prealbumin Proteins 0.000 description 7
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
102000009190 Transthyretin Human genes 0.000 description 7
125000003282 alkyl amino group Chemical group 0.000 description 7
DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 7
125000004429 atom Chemical group 0.000 description 7
210000004369 blood Anatomy 0.000 description 7
239000008280 blood Substances 0.000 description 7
230000015556 catabolic process Effects 0.000 description 7
238000003776 cleavage reaction Methods 0.000 description 7
125000004093 cyano group Chemical group *C#N 0.000 description 7
238000001727 in vivo Methods 0.000 description 7
201000008319 inclusion body myositis Diseases 0.000 description 7
230000004054 inflammatory process Effects 0.000 description 7
210000004153 islets of langerhan Anatomy 0.000 description 7
239000008101 lactose Substances 0.000 description 7
239000002502 liposome Substances 0.000 description 7
239000000314 lubricant Substances 0.000 description 7
230000004048 modification Effects 0.000 description 7
238000012986 modification Methods 0.000 description 7
201000001119 neuropathy Diseases 0.000 description 7
230000007823 neuropathy Effects 0.000 description 7
239000002243 precursor Substances 0.000 description 7
230000007017 scission Effects 0.000 description 7
239000000126 substance Substances 0.000 description 7
239000011593 sulfur Substances 0.000 description 7
230000002459 sustained effect Effects 0.000 description 7
208000035143 Bacterial infection Diseases 0.000 description 6
206010016207 Familial Mediterranean fever Diseases 0.000 description 6
108010010803 Gelatin Proteins 0.000 description 6
102100025818 Major prion protein Human genes 0.000 description 6
VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 6
102000029797 Prion Human genes 0.000 description 6
108091000054 Prion Proteins 0.000 description 6
229920006397 acrylic thermoplastic Polymers 0.000 description 6
150000001408 amides Chemical class 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
208000022362 bacterial infectious disease Diseases 0.000 description 6
230000008499 blood brain barrier function Effects 0.000 description 6
210000001218 blood-brain barrier Anatomy 0.000 description 6
DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 6
230000006378 damage Effects 0.000 description 6
238000006731 degradation reaction Methods 0.000 description 6
239000003937 drug carrier Substances 0.000 description 6
239000008273 gelatin Substances 0.000 description 6
229920000159 gelatin Polymers 0.000 description 6
235000019322 gelatine Nutrition 0.000 description 6
235000011852 gelatine desserts Nutrition 0.000 description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
230000000670 limiting effect Effects 0.000 description 6
125000004433 nitrogen atom Chemical group N* 0.000 description 6
229940068196 placebo Drugs 0.000 description 6
239000000902 placebo Substances 0.000 description 6
229920003229 poly(methyl methacrylate) Polymers 0.000 description 6
239000000651 prodrug Substances 0.000 description 6
229940002612 prodrug Drugs 0.000 description 6
208000011580 syndromic disease Diseases 0.000 description 6
ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 6
206010008111 Cerebral haemorrhage Diseases 0.000 description 5
108020004705 Codon Proteins 0.000 description 5
208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 5
208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 5
239000001856 Ethyl cellulose Substances 0.000 description 5
101000617536 Homo sapiens Presenilin-1 Proteins 0.000 description 5
208000022435 Light chain deposition disease Diseases 0.000 description 5
208000002193 Pain Diseases 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
238000004220 aggregation Methods 0.000 description 5
125000002723 alicyclic group Chemical group 0.000 description 5
239000003963 antioxidant agent Substances 0.000 description 5
235000006708 antioxidants Nutrition 0.000 description 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 5
229920002301 cellulose acetate Polymers 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
230000001684 chronic effect Effects 0.000 description 5
230000001419 dependent effect Effects 0.000 description 5
238000011161 development Methods 0.000 description 5
230000018109 developmental process Effects 0.000 description 5
239000006185 dispersion Substances 0.000 description 5
230000004064 dysfunction Effects 0.000 description 5
239000003995 emulsifying agent Substances 0.000 description 5
235000019325 ethyl cellulose Nutrition 0.000 description 5
229920001249 ethyl cellulose Polymers 0.000 description 5
239000000945 filler Substances 0.000 description 5
239000007903 gelatin capsule Substances 0.000 description 5
230000003834 intracellular effect Effects 0.000 description 5
210000003734 kidney Anatomy 0.000 description 5
230000003902 lesion Effects 0.000 description 5
239000007788 liquid Substances 0.000 description 5
230000007246 mechanism Effects 0.000 description 5
229910021645 metal ion Inorganic materials 0.000 description 5
210000002569 neuron Anatomy 0.000 description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
210000000496 pancreas Anatomy 0.000 description 5
239000002245 particle Substances 0.000 description 5
239000006187 pill Substances 0.000 description 5
208000022256 primary systemic amyloidosis Diseases 0.000 description 5
230000008569 process Effects 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
125000006413 ring segment Chemical group 0.000 description 5
239000002904 solvent Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
230000009885 systemic effect Effects 0.000 description 5
231100000331 toxic Toxicity 0.000 description 5
230000002588 toxic effect Effects 0.000 description 5
231100000419 toxicity Toxicity 0.000 description 5
239000000080 wetting agent Substances 0.000 description 5
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
101150079978 AGRN gene Proteins 0.000 description 4
208000020687 AH amyloidosis Diseases 0.000 description 4
102100040026 Agrin Human genes 0.000 description 4
108700019743 Agrin Proteins 0.000 description 4
102000005666 Apolipoprotein A-I Human genes 0.000 description 4
108010059886 Apolipoprotein A-I Proteins 0.000 description 4
241000894006 Bacteria Species 0.000 description 4
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 4
206010016202 Familial Amyloidosis Diseases 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
208000032843 Hemorrhage Diseases 0.000 description 4
241000282412 Homo Species 0.000 description 4
101000772194 Homo sapiens Transthyretin Proteins 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
206010028980 Neoplasm Diseases 0.000 description 4
206010029240 Neuritis Diseases 0.000 description 4
239000002202 Polyethylene glycol Substances 0.000 description 4
208000024777 Prion disease Diseases 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
206010039811 Secondary amyloidosis Diseases 0.000 description 4
102100029290 Transthyretin Human genes 0.000 description 4
206010044688 Trisomy 21 Diseases 0.000 description 4
206010047700 Vomiting Diseases 0.000 description 4
125000004442 acylamino group Chemical group 0.000 description 4
230000002411 adverse Effects 0.000 description 4
206010064930 age-related macular degeneration Diseases 0.000 description 4
230000002776 aggregation Effects 0.000 description 4
238000010171 animal model Methods 0.000 description 4
230000008901 benefit Effects 0.000 description 4
239000011230 binding agent Substances 0.000 description 4
230000000740 bleeding effect Effects 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
239000011247 coating layer Substances 0.000 description 4
230000034994 death Effects 0.000 description 4
238000003745 diagnosis Methods 0.000 description 4
238000000502 dialysis Methods 0.000 description 4
MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 4
208000015756 familial Alzheimer disease Diseases 0.000 description 4
235000011187 glycerol Nutrition 0.000 description 4
239000008187 granular material Substances 0.000 description 4
239000003701 inert diluent Substances 0.000 description 4
210000000936 intestine Anatomy 0.000 description 4
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
208000017169 kidney disease Diseases 0.000 description 4
210000004185 liver Anatomy 0.000 description 4
201000000050 myeloid neoplasm Diseases 0.000 description 4
239000003921 oil Substances 0.000 description 4
150000002894 organic compounds Chemical class 0.000 description 4
230000001575 pathological effect Effects 0.000 description 4
230000035515 penetration Effects 0.000 description 4
229920001184 polypeptide Polymers 0.000 description 4
239000003755 preservative agent Substances 0.000 description 4
230000001737 promoting effect Effects 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
150000003384 small molecules Chemical class 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000011734 sodium Substances 0.000 description 4
159000000000 sodium salts Chemical class 0.000 description 4
229940045902 sodium stearyl fumarate Drugs 0.000 description 4
239000007787 solid Substances 0.000 description 4
239000007909 solid dosage form Substances 0.000 description 4
238000006467 substitution reaction Methods 0.000 description 4
150000008163 sugars Chemical class 0.000 description 4
239000000725 suspension Substances 0.000 description 4
239000000454 talc Substances 0.000 description 4
229910052623 talc Inorganic materials 0.000 description 4
235000012222 talc Nutrition 0.000 description 4
150000003573 thiols Chemical class 0.000 description 4
238000002054 transplantation Methods 0.000 description 4
239000001993 wax Substances 0.000 description 4
244000215068 Acacia senegal Species 0.000 description 3
229920001817 Agar Polymers 0.000 description 3
241000416162 Astragalus gummifer Species 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
102000055006 Calcitonin Human genes 0.000 description 3
108060001064 Calcitonin Proteins 0.000 description 3
241000282472 Canis lupus familiaris Species 0.000 description 3
241000282693 Cercopithecidae Species 0.000 description 3
208000028698 Cognitive impairment Diseases 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 description 3
241000282326 Felis catus Species 0.000 description 3
206010016654 Fibrosis Diseases 0.000 description 3
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
102000003886 Glycoproteins Human genes 0.000 description 3
108090000288 Glycoproteins Proteins 0.000 description 3
229920000084 Gum arabic Polymers 0.000 description 3
102000015779 HDL Lipoproteins Human genes 0.000 description 3
108010010234 HDL Lipoproteins Proteins 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
206010022489 Insulin Resistance Diseases 0.000 description 3
208000008574 Intracranial Hemorrhages Diseases 0.000 description 3
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
229930195725 Mannitol Natural products 0.000 description 3
102000012750 Membrane Glycoproteins Human genes 0.000 description 3
108010090054 Membrane Glycoproteins Proteins 0.000 description 3
102100040243 Microtubule-associated protein tau Human genes 0.000 description 3
102000016943 Muramidase Human genes 0.000 description 3
108010014251 Muramidase Proteins 0.000 description 3
108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 3
206010028813 Nausea Diseases 0.000 description 3
241001494479 Pecora Species 0.000 description 3
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
102000054727 Serum Amyloid A Human genes 0.000 description 3
101710190759 Serum amyloid A protein Proteins 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
229920001615 Tragacanth Polymers 0.000 description 3
241000700605 Viruses Species 0.000 description 3
208000027418 Wounds and injury Diseases 0.000 description 3
230000002159 abnormal effect Effects 0.000 description 3
238000010521 absorption reaction Methods 0.000 description 3
235000010489 acacia gum Nutrition 0.000 description 3
239000000205 acacia gum Substances 0.000 description 3
230000009471 action Effects 0.000 description 3
125000002252 acyl group Chemical group 0.000 description 3
235000010419 agar Nutrition 0.000 description 3
230000032683 aging Effects 0.000 description 3
235000010443 alginic acid Nutrition 0.000 description 3
229920000615 alginic acid Polymers 0.000 description 3
125000004947 alkyl aryl amino group Chemical group 0.000 description 3
101150031224 app gene Proteins 0.000 description 3
125000001769 aryl amino group Chemical group 0.000 description 3
125000005199 aryl carbonyloxy group Chemical group 0.000 description 3
125000005110 aryl thio group Chemical group 0.000 description 3
125000005200 aryloxy carbonyloxy group Chemical group 0.000 description 3
238000003556 assay Methods 0.000 description 3
230000001746 atrial effect Effects 0.000 description 3
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
210000004204 blood vessel Anatomy 0.000 description 3
BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 3
229960004015 calcitonin Drugs 0.000 description 3
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 3
235000013539 calcium stearate Nutrition 0.000 description 3
239000008116 calcium stearate Substances 0.000 description 3
201000011510 cancer Diseases 0.000 description 3
150000001721 carbon Chemical group 0.000 description 3
210000003169 central nervous system Anatomy 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000003086 colorant Substances 0.000 description 3
206010011005 corneal dystrophy Diseases 0.000 description 3
229940109239 creatinine Drugs 0.000 description 3
230000002939 deleterious effect Effects 0.000 description 3
125000004663 dialkyl amino group Chemical group 0.000 description 3
125000004986 diarylamino group Chemical group 0.000 description 3
235000014113 dietary fatty acids Nutrition 0.000 description 3
230000008030 elimination Effects 0.000 description 3
238000003379 elimination reaction Methods 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
229940088598 enzyme Drugs 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000013265 extended release Methods 0.000 description 3
201000006061 fatal familial insomnia Diseases 0.000 description 3
239000000194 fatty acid Substances 0.000 description 3
229930195729 fatty acid Natural products 0.000 description 3
230000003619 fibrillary effect Effects 0.000 description 3
230000004761 fibrosis Effects 0.000 description 3
210000001035 gastrointestinal tract Anatomy 0.000 description 3
238000001631 haemodialysis Methods 0.000 description 3
210000002216 heart Anatomy 0.000 description 3
208000019855 heavy chain deposition disease Diseases 0.000 description 3
230000000322 hemodialysis Effects 0.000 description 3
229940088597 hormone Drugs 0.000 description 3
239000005556 hormone Substances 0.000 description 3
201000001421 hyperglycemia Diseases 0.000 description 3
239000012729 immediate-release (IR) formulation Substances 0.000 description 3
125000001041 indolyl group Chemical group 0.000 description 3
208000015181 infectious disease Diseases 0.000 description 3
208000014674 injury Diseases 0.000 description 3
230000007794 irritation Effects 0.000 description 3
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
239000000594 mannitol Substances 0.000 description 3
235000010355 mannitol Nutrition 0.000 description 3
238000004949 mass spectrometry Methods 0.000 description 3
230000004060 metabolic process Effects 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
210000000274 microglia Anatomy 0.000 description 3
238000000465 moulding Methods 0.000 description 3
230000008693 nausea Effects 0.000 description 3
210000005036 nerve Anatomy 0.000 description 3
230000007935 neutral effect Effects 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
201000008482 osteoarthritis Diseases 0.000 description 3
230000036961 partial effect Effects 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
239000004014 plasticizer Substances 0.000 description 3
125000003367 polycyclic group Chemical group 0.000 description 3
239000004848 polyfunctional curative Substances 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
229960004063 propylene glycol Drugs 0.000 description 3
235000013772 propylene glycol Nutrition 0.000 description 3
125000004076 pyridyl group Chemical group 0.000 description 3
206010039073 rheumatoid arthritis Diseases 0.000 description 3
230000003248 secreting effect Effects 0.000 description 3
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 3
235000012239 silicon dioxide Nutrition 0.000 description 3
235000010356 sorbitol Nutrition 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
210000000952 spleen Anatomy 0.000 description 3
230000006641 stabilisation Effects 0.000 description 3
238000011105 stabilization Methods 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
125000001544 thienyl group Chemical group 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
235000010487 tragacanth Nutrition 0.000 description 3
239000000196 tragacanth Substances 0.000 description 3
229940116362 tragacanth Drugs 0.000 description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
230000009278 visceral effect Effects 0.000 description 3
229920003176 water-insoluble polymer Polymers 0.000 description 3
208000027121 wild type ATTR amyloidosis Diseases 0.000 description 3
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
208000000044 Amnesia Diseases 0.000 description 2
241000272517 Anseriformes Species 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
101800001288 Atrial natriuretic factor Proteins 0.000 description 2
102400001282 Atrial natriuretic peptide Human genes 0.000 description 2
101800001890 Atrial natriuretic peptide Proteins 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
208000014644 Brain disease Diseases 0.000 description 2
239000004322 Butylated hydroxytoluene Substances 0.000 description 2
NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
201000000166 CST3-related cerebral amyloid angiopathy Diseases 0.000 description 2
241000283707 Capra Species 0.000 description 2
101710132601 Capsid protein Proteins 0.000 description 2
208000031229 Cardiomyopathies Diseases 0.000 description 2
229920000623 Cellulose acetate phthalate Polymers 0.000 description 2
229920008347 Cellulose acetate propionate Polymers 0.000 description 2
102000008186 Collagen Human genes 0.000 description 2
108010035532 Collagen Proteins 0.000 description 2
102000004266 Collagen Type IV Human genes 0.000 description 2
108010042086 Collagen Type IV Proteins 0.000 description 2
208000019736 Cranial nerve disease Diseases 0.000 description 2
229920002785 Croscarmellose sodium Polymers 0.000 description 2
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
206010011878 Deafness Diseases 0.000 description 2
206010012735 Diarrhoea Diseases 0.000 description 2
206010061818 Disease progression Diseases 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
208000032274 Encephalopathy Diseases 0.000 description 2
102000016359 Fibronectins Human genes 0.000 description 2
108010067306 Fibronectins Proteins 0.000 description 2
241000206672 Gelidium Species 0.000 description 2
206010018341 Gliosis Diseases 0.000 description 2
208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 description 2
239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
102000013463 Immunoglobulin Light Chains Human genes 0.000 description 2
108010065825 Immunoglobulin Light Chains Proteins 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
206010023230 Joint stiffness Diseases 0.000 description 2
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
102000007547 Laminin Human genes 0.000 description 2
108010085895 Laminin Proteins 0.000 description 2
208000026139 Memory disease Diseases 0.000 description 2
208000034578 Multiple myelomas Diseases 0.000 description 2
206010029350 Neurotoxicity Diseases 0.000 description 2
BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
102000035195 Peptidases Human genes 0.000 description 2
108091005804 Peptidases Proteins 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
108010050254 Presenilins Proteins 0.000 description 2
102000015499 Presenilins Human genes 0.000 description 2
206010036673 Primary amyloidosis Diseases 0.000 description 2
ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
239000004365 Protease Substances 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
206010062237 Renal impairment Diseases 0.000 description 2
101100379247 Salmo trutta apoa1 gene Proteins 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
206010044221 Toxic encephalopathy Diseases 0.000 description 2
DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 2
208000024780 Urticaria Diseases 0.000 description 2
238000002441 X-ray diffraction Methods 0.000 description 2
240000008042 Zea mays Species 0.000 description 2
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
235000002017 Zea mays subsp mays Nutrition 0.000 description 2
229920002494 Zein Polymers 0.000 description 2
108010055615 Zein Proteins 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
230000023445 activated T cell autonomous cell death Effects 0.000 description 2
210000001642 activated microglia Anatomy 0.000 description 2
239000008186 active pharmaceutical agent Substances 0.000 description 2
239000000783 alginic acid Substances 0.000 description 2
229960001126 alginic acid Drugs 0.000 description 2
150000004781 alginic acids Chemical class 0.000 description 2
125000006323 alkenyl amino group Chemical group 0.000 description 2
125000003302 alkenyloxy group Chemical group 0.000 description 2
125000005108 alkenylthio group Chemical group 0.000 description 2
125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 2
125000002877 alkyl aryl group Chemical group 0.000 description 2
125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
125000005196 alkyl carbonyloxy group Chemical group 0.000 description 2
125000004691 alkyl thio carbonyl group Chemical group 0.000 description 2
125000004414 alkyl thio group Chemical group 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
229910052782 aluminium Inorganic materials 0.000 description 2
WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
150000001412 amines Chemical group 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
230000000844 anti-bacterial effect Effects 0.000 description 2
239000003429 antifungal agent Substances 0.000 description 2
229940121375 antifungal agent Drugs 0.000 description 2
210000002565 arteriole Anatomy 0.000 description 2
210000001367 artery Anatomy 0.000 description 2
125000004658 aryl carbonyl amino group Chemical group 0.000 description 2
125000004104 aryloxy group Chemical group 0.000 description 2
208000037875 astrocytosis Diseases 0.000 description 2
230000007341 astrogliosis Effects 0.000 description 2
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 2
210000003719 b-lymphocyte Anatomy 0.000 description 2
230000004888 barrier function Effects 0.000 description 2
210000002469 basement membrane Anatomy 0.000 description 2
235000012216 bentonite Nutrition 0.000 description 2
239000000440 bentonite Substances 0.000 description 2
229910000278 bentonite Inorganic materials 0.000 description 2
SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical group CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 2
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
230000033228 biological regulation Effects 0.000 description 2
210000004958 brain cell Anatomy 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
229940095259 butylated hydroxytoluene Drugs 0.000 description 2
229910000019 calcium carbonate Inorganic materials 0.000 description 2
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
150000007942 carboxylates Chemical class 0.000 description 2
NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 2
230000005779 cell damage Effects 0.000 description 2
208000037887 cell injury Diseases 0.000 description 2
230000007541 cellular toxicity Effects 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
229920006217 cellulose acetate butyrate Polymers 0.000 description 2
229940081734 cellulose acetate phthalate Drugs 0.000 description 2
210000003710 cerebral cortex Anatomy 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
230000002759 chromosomal effect Effects 0.000 description 2
208000037976 chronic inflammation Diseases 0.000 description 2
238000004140 cleaning Methods 0.000 description 2
229920001436 collagen Polymers 0.000 description 2
IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 2
235000005822 corn Nutrition 0.000 description 2
235000012343 cottonseed oil Nutrition 0.000 description 2
239000002385 cottonseed oil Substances 0.000 description 2
208000014826 cranial nerve neuropathy Diseases 0.000 description 2
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 2
150000001925 cycloalkenes Chemical class 0.000 description 2
ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 2
235000018417 cysteine Nutrition 0.000 description 2
229960002433 cysteine Drugs 0.000 description 2
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
231100000895 deafness Toxicity 0.000 description 2
230000007850 degeneration Effects 0.000 description 2
230000005750 disease progression Effects 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
239000008298 dragée Substances 0.000 description 2
239000000975 dye Substances 0.000 description 2
230000002124 endocrine Effects 0.000 description 2
230000002708 enhancing effect Effects 0.000 description 2
125000004185 ester group Chemical group 0.000 description 2
MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
210000001723 extracellular space Anatomy 0.000 description 2
210000003414 extremity Anatomy 0.000 description 2
235000019197 fats Nutrition 0.000 description 2
150000004665 fatty acids Chemical class 0.000 description 2
239000000835 fiber Substances 0.000 description 2
239000007888 film coating Substances 0.000 description 2
238000009501 film coating Methods 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
239000012530 fluid Substances 0.000 description 2
230000009246 food effect Effects 0.000 description 2
235000021471 food effect Nutrition 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
239000008103 glucose Substances 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
208000016354 hearing loss disease Diseases 0.000 description 2
210000005003 heart tissue Anatomy 0.000 description 2
230000000971 hippocampal effect Effects 0.000 description 2
235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
239000001863 hydroxypropyl cellulose Substances 0.000 description 2
238000003384 imaging method Methods 0.000 description 2
239000007943 implant Substances 0.000 description 2
238000010348 incorporation Methods 0.000 description 2
229940060367 inert ingredients Drugs 0.000 description 2
238000002329 infrared spectrum Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
238000011835 investigation Methods 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
230000003907 kidney function Effects 0.000 description 2
201000003775 lattice corneal dystrophy Diseases 0.000 description 2
125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
239000008297 liquid dosage form Substances 0.000 description 2
230000007774 longterm Effects 0.000 description 2
238000002595 magnetic resonance imaging Methods 0.000 description 2
238000005259 measurement Methods 0.000 description 2
230000006984 memory degeneration Effects 0.000 description 2
208000023060 memory loss Diseases 0.000 description 2
210000002418 meninge Anatomy 0.000 description 2
230000006996 mental state Effects 0.000 description 2
IQSHMXAZFHORGY-UHFFFAOYSA-N methyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound COC(=O)C=C.CC(=C)C(O)=O IQSHMXAZFHORGY-UHFFFAOYSA-N 0.000 description 2
230000000813 microbial effect Effects 0.000 description 2
239000007912 modified release tablet Substances 0.000 description 2
230000000877 morphologic effect Effects 0.000 description 2
210000001087 myotubule Anatomy 0.000 description 2
210000004898 n-terminal fragment Anatomy 0.000 description 2
210000002241 neurite Anatomy 0.000 description 2
208000015122 neurodegenerative disease Diseases 0.000 description 2
210000002682 neurofibrillary tangle Anatomy 0.000 description 2
230000016273 neuron death Effects 0.000 description 2
230000002981 neuropathic effect Effects 0.000 description 2
230000007135 neurotoxicity Effects 0.000 description 2
231100000228 neurotoxicity Toxicity 0.000 description 2
239000004006 olive oil Substances 0.000 description 2
235000008390 olive oil Nutrition 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
230000008506 pathogenesis Effects 0.000 description 2
230000007170 pathology Effects 0.000 description 2
230000002093 peripheral effect Effects 0.000 description 2
210000000578 peripheral nerve Anatomy 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
150000004804 polysaccharides Polymers 0.000 description 2
229920002689 polyvinyl acetate Polymers 0.000 description 2
231100000857 poor renal function Toxicity 0.000 description 2
239000011148 porous material Substances 0.000 description 2
238000012545 processing Methods 0.000 description 2
230000000750 progressive effect Effects 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
210000004129 prosencephalon Anatomy 0.000 description 2
239000011241 protective layer Substances 0.000 description 2
230000012846 protein folding Effects 0.000 description 2
230000006337 proteolytic cleavage Effects 0.000 description 2
230000010349 pulsation Effects 0.000 description 2
239000008213 purified water Substances 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
125000000719 pyrrolidinyl group Chemical group 0.000 description 2
125000000168 pyrrolyl group Chemical group 0.000 description 2
238000011002 quantification Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
230000004044 response Effects 0.000 description 2
210000003583 retinal pigment epithelium Anatomy 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
229930195734 saturated hydrocarbon Natural products 0.000 description 2
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
239000008159 sesame oil Substances 0.000 description 2
235000011803 sesame oil Nutrition 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
235000019333 sodium laurylsulphate Nutrition 0.000 description 2
239000008109 sodium starch glycolate Substances 0.000 description 2
229920003109 sodium starch glycolate Polymers 0.000 description 2
229940079832 sodium starch glycolate Drugs 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
239000008247 solid mixture Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 2
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
238000013269 sustained drug release Methods 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
230000008961 swelling Effects 0.000 description 2
239000007916 tablet composition Substances 0.000 description 2
230000004797 therapeutic response Effects 0.000 description 2
208000013077 thyroid gland carcinoma Diseases 0.000 description 2
230000009466 transformation Effects 0.000 description 2
238000000844 transformation Methods 0.000 description 2
230000009261 transgenic effect Effects 0.000 description 2
URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
239000001069 triethyl citrate Substances 0.000 description 2
VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 2
235000013769 triethyl citrate Nutrition 0.000 description 2
201000008827 tuberculosis Diseases 0.000 description 2
210000002700 urine Anatomy 0.000 description 2
210000003462 vein Anatomy 0.000 description 2
230000008673 vomiting Effects 0.000 description 2
210000000707 wrist Anatomy 0.000 description 2
QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 1
125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
125000006729 (C2-C5) alkenyl group Chemical group 0.000 description 1
125000006730 (C2-C5) alkynyl group Chemical group 0.000 description 1
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical group C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
229940058015 1,3-butylene glycol Drugs 0.000 description 1
FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical group N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
JNODDICFTDYODH-UHFFFAOYSA-N 2-hydroxytetrahydrofuran Chemical compound OC1CCCO1 JNODDICFTDYODH-UHFFFAOYSA-N 0.000 description 1
DSIHEWRAJBNNLQ-UHFFFAOYSA-N 3-(4-phenyl-3,6-dihydro-2h-pyridin-1-yl)propane-1-sulfonic acid Chemical compound C1N(CCCS(=O)(=O)O)CCC(C=2C=CC=CC=2)=C1 DSIHEWRAJBNNLQ-UHFFFAOYSA-N 0.000 description 1
VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 description 1
PEPBFCOIJRULGJ-UHFFFAOYSA-N 3h-1,2,3-benzodioxazole Chemical group C1=CC=C2NOOC2=C1 PEPBFCOIJRULGJ-UHFFFAOYSA-N 0.000 description 1
SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
208000024667 ABeta amyloidosis, Dutch type Diseases 0.000 description 1
208000023697 ABri amyloidosis Diseases 0.000 description 1
208000017227 ADan amyloidosis Diseases 0.000 description 1
QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 description 1
102100033639 Acetylcholinesterase Human genes 0.000 description 1
108010022752 Acetylcholinesterase Proteins 0.000 description 1
229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
206010048998 Acute phase reaction Diseases 0.000 description 1
102100034112 Alkyldihydroxyacetonephosphate synthase, peroxisomal Human genes 0.000 description 1
108700028369 Alleles Proteins 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
235000009051 Ambrosia paniculata var. peruviana Nutrition 0.000 description 1
102000018430 Amyloid-beta precursor proteins Human genes 0.000 description 1
108050007552 Amyloid-beta precursor proteins Proteins 0.000 description 1
241000272525 Anas platyrhynchos Species 0.000 description 1
206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
102000009081 Apolipoprotein A-II Human genes 0.000 description 1
108010087614 Apolipoprotein A-II Proteins 0.000 description 1
108010060159 Apolipoprotein E4 Proteins 0.000 description 1
108010071619 Apolipoproteins Proteins 0.000 description 1
102000007592 Apolipoproteins Human genes 0.000 description 1
235000017060 Arachis glabrata Nutrition 0.000 description 1
244000105624 Arachis hypogaea Species 0.000 description 1
235000010777 Arachis hypogaea Nutrition 0.000 description 1
235000018262 Arachis monticola Nutrition 0.000 description 1
235000003097 Artemisia absinthium Nutrition 0.000 description 1
240000001851 Artemisia dracunculus Species 0.000 description 1
235000017731 Artemisia dracunculus ssp. dracunculus Nutrition 0.000 description 1
235000003261 Artemisia vulgaris Nutrition 0.000 description 1
206010003210 Arteriosclerosis Diseases 0.000 description 1
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
206010061666 Autonomic neuropathy Diseases 0.000 description 1
230000007082 Aβ accumulation Effects 0.000 description 1
206010004146 Basal cell carcinoma Diseases 0.000 description 1
208000027496 Behcet disease Diseases 0.000 description 1
208000009137 Behcet syndrome Diseases 0.000 description 1
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical group OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
SESFRYSPDFLNCH-UHFFFAOYSA-N Benzyl benzoate Natural products C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 1
102100021257 Beta-secretase 1 Human genes 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
201000004569 Blindness Diseases 0.000 description 1
229940123923 Butyrylcholinesterase inhibitor Drugs 0.000 description 1
108010075254 C-Peptide Proteins 0.000 description 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
101100016363 Caenorhabditis elegans his-67 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
201000009030 Carcinoma Diseases 0.000 description 1
208000020446 Cardiac disease Diseases 0.000 description 1
208000005024 Castleman disease Diseases 0.000 description 1
241000606161 Chlamydia Species 0.000 description 1
229920001287 Chondroitin sulfate Polymers 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
102000012192 Cystatin C Human genes 0.000 description 1
108010061642 Cystatin C Proteins 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
108020004414 DNA Proteins 0.000 description 1
208000031124 Dementia Alzheimer type Diseases 0.000 description 1
229920000045 Dermatan sulfate Polymers 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
241000283073 Equus caballus Species 0.000 description 1
102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
108050001049 Extracellular proteins Proteins 0.000 description 1
108010049003 Fibrinogen Proteins 0.000 description 1
102000008946 Fibrinogen Human genes 0.000 description 1
239000004606 Fillers/Extenders Substances 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
241000287828 Gallus gallus Species 0.000 description 1
206010064571 Gene mutation Diseases 0.000 description 1
208000003736 Gerstmann-Straussler-Scheinker Disease Diseases 0.000 description 1
206010072075 Gerstmann-Straussler-Scheinker syndrome Diseases 0.000 description 1
244000194101 Ginkgo biloba Species 0.000 description 1
235000008100 Ginkgo biloba Nutrition 0.000 description 1
102000006395 Globulins Human genes 0.000 description 1
108010044091 Globulins Proteins 0.000 description 1
235000010469 Glycine max Nutrition 0.000 description 1
241000282575 Gorilla Species 0.000 description 1
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
206010019280 Heart failures Diseases 0.000 description 1
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
208000003923 Hereditary Corneal Dystrophies Diseases 0.000 description 1
239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
208000017604 Hodgkin disease Diseases 0.000 description 1
208000021519 Hodgkin lymphoma Diseases 0.000 description 1
208000010747 Hodgkins lymphoma Diseases 0.000 description 1
101000799143 Homo sapiens Alkyldihydroxyacetonephosphate synthase, peroxisomal Proteins 0.000 description 1
101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 1
101000617546 Homo sapiens Presenilin-2 Proteins 0.000 description 1
101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 1
208000035150 Hypercholesterolemia Diseases 0.000 description 1
201000000162 ITM2B-related cerebral amyloid angiopathy 1 Diseases 0.000 description 1
201000000194 ITM2B-related cerebral amyloid angiopathy 2 Diseases 0.000 description 1
108060003951 Immunoglobulin Proteins 0.000 description 1
108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
208000026350 Inborn Genetic disease Diseases 0.000 description 1
108010002352 Interleukin-1 Proteins 0.000 description 1
108090001005 Interleukin-6 Proteins 0.000 description 1
206010023232 Joint swelling Diseases 0.000 description 1
208000003456 Juvenile Arthritis Diseases 0.000 description 1
206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
229920000288 Keratan sulfate Polymers 0.000 description 1
QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
241001676635 Lepidorhombus whiffiagonis Species 0.000 description 1
206010024229 Leprosy Diseases 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
229920002774 Maltodextrin Polymers 0.000 description 1
239000005913 Maltodextrin Substances 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
229920003091 Methocel™ Polymers 0.000 description 1
102000029749 Microtubule Human genes 0.000 description 1
108091022875 Microtubule Proteins 0.000 description 1
229920000881 Modified starch Polymers 0.000 description 1
241000699660 Mus musculus Species 0.000 description 1
241000238367 Mya arenaria Species 0.000 description 1
GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
240000007817 Olea europaea Species 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
206010031252 Osteomyelitis Diseases 0.000 description 1
241000237502 Ostreidae Species 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
241000282577 Pan troglodytes Species 0.000 description 1
206010033733 Papule Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
102000015731 Peptide Hormones Human genes 0.000 description 1
108010038988 Peptide Hormones Proteins 0.000 description 1
241000577979 Peromyscus spicilegus Species 0.000 description 1
208000037581 Persistent Infection Diseases 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
101000612288 Pinus strobus Putative oxygen-evolving enhancer protein 1 Proteins 0.000 description 1
208000021161 Plasma cell disease Diseases 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
239000004952 Polyamide Substances 0.000 description 1
229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
241000288906 Primates Species 0.000 description 1
229920003110 Primojel Polymers 0.000 description 1
108010076181 Proinsulin Proteins 0.000 description 1
102000003946 Prolactin Human genes 0.000 description 1
108010057464 Prolactin Proteins 0.000 description 1
206010036832 Prolactinoma Diseases 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
208000028017 Psychotic disease Diseases 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
241000700159 Rattus Species 0.000 description 1
208000033464 Reiter syndrome Diseases 0.000 description 1
208000001647 Renal Insufficiency Diseases 0.000 description 1
206010038389 Renal cancer Diseases 0.000 description 1
206010038748 Restrictive cardiomyopathy Diseases 0.000 description 1
XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
201000010848 Schnitzler Syndrome Diseases 0.000 description 1
241000555745 Sciuridae Species 0.000 description 1
206010039966 Senile dementia Diseases 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
206010040738 Sinus arrest Diseases 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
241000282898 Sus scrofa Species 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
206010044565 Tremor Diseases 0.000 description 1
241000282458 Ursus sp. Species 0.000 description 1
208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 description 1
FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
229930003427 Vitamin E Natural products 0.000 description 1
208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
208000016463 Wild type ABeta2M amyloidosis Diseases 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
TYVWBCMQECJNSK-UHFFFAOYSA-N [2-methyl-3-(2-methylprop-2-enoyloxy)butan-2-yl]azanium;chloride Chemical compound [Cl-].CC([NH3+])(C)C(C)OC(=O)C(C)=C TYVWBCMQECJNSK-UHFFFAOYSA-N 0.000 description 1
230000005856 abnormality Effects 0.000 description 1
239000002250 absorbent Substances 0.000 description 1
230000002745 absorbent Effects 0.000 description 1
239000003655 absorption accelerator Substances 0.000 description 1
239000003070 absorption delaying agent Substances 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
229960001138 acetylsalicylic acid Drugs 0.000 description 1
238000001994 activation Methods 0.000 description 1
125000002015 acyclic group Chemical group 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
125000005233 alkylalcohol group Chemical group 0.000 description 1
FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
229940087168 alpha tocopherol Drugs 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
230000007450 amyloidogenic pathway Effects 0.000 description 1
210000003484 anatomy Anatomy 0.000 description 1
238000000848 angular dependent Auger electron spectroscopy Methods 0.000 description 1
239000000427 antigen Substances 0.000 description 1
102000036639 antigens Human genes 0.000 description 1
108091007433 antigens Proteins 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000003435 aroyl group Chemical group 0.000 description 1
239000001138 artemisia absinthium Substances 0.000 description 1
208000011775 arteriosclerosis disease Diseases 0.000 description 1
125000004350 aryl cycloalkyl group Chemical group 0.000 description 1
125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
235000010385 ascorbyl palmitate Nutrition 0.000 description 1
238000011914 asymmetric synthesis Methods 0.000 description 1
229910052788 barium Inorganic materials 0.000 description 1
DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
229960002903 benzyl benzoate Drugs 0.000 description 1
108091007737 beta-secretases Proteins 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin Substances 0.000 description 1
208000034158 bleeding Diseases 0.000 description 1
230000036765 blood level Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
208000005881 bovine spongiform encephalopathy Diseases 0.000 description 1
208000025698 brain inflammatory disease Diseases 0.000 description 1
235000021152 breakfast Nutrition 0.000 description 1
201000009267 bronchiectasis Diseases 0.000 description 1
239000006189 buccal tablet Substances 0.000 description 1
239000013590 bulk material Substances 0.000 description 1
235000019437 butane-1,3-diol Nutrition 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
239000000378 calcium silicate Substances 0.000 description 1
229910052918 calcium silicate Inorganic materials 0.000 description 1
OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
239000007894 caplet Substances 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
208000003295 carpal tunnel syndrome Diseases 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
239000004359 castor oil Substances 0.000 description 1
235000019438 castor oil Nutrition 0.000 description 1
230000001364 causal effect Effects 0.000 description 1
238000000423 cell based assay Methods 0.000 description 1
230000030833 cell death Effects 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
229960000541 cetyl alcohol Drugs 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
235000013330 chicken meat Nutrition 0.000 description 1
229960004926 chlorobutanol Drugs 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
229940059329 chondroitin sulfate Drugs 0.000 description 1
210000002987 choroid plexus Anatomy 0.000 description 1
208000019902 chronic diarrheal disease Diseases 0.000 description 1
230000006020 chronic inflammation Effects 0.000 description 1
208000037893 chronic inflammatory disorder Diseases 0.000 description 1
239000004927 clay Substances 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
230000006999 cognitive decline Effects 0.000 description 1
239000008119 colloidal silica Substances 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
238000009500 colour coating Methods 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
230000009850 completed effect Effects 0.000 description 1
239000007891 compressed tablet Substances 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
238000010276 construction Methods 0.000 description 1
230000008602 contraction Effects 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
239000012792 core layer Substances 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
230000000875 corresponding effect Effects 0.000 description 1
125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
239000006071 cream Substances 0.000 description 1
125000006165 cyclic alkyl group Chemical group 0.000 description 1
125000000392 cycloalkenyl group Chemical group 0.000 description 1
125000006448 cycloalkyl cycloalkyl group Chemical group 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
KDUIUFJBNGTBMD-VXMYFEMYSA-N cyclooctatetraene Chemical compound C1=C\C=C/C=C\C=C1 KDUIUFJBNGTBMD-VXMYFEMYSA-N 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
229960001305 cysteine hydrochloride Drugs 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
230000006735 deficit Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 1
229940051593 dermatan sulfate Drugs 0.000 description 1
238000013461 design Methods 0.000 description 1
239000003599 detergent Substances 0.000 description 1
230000006866 deterioration Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
238000002405 diagnostic procedure Methods 0.000 description 1
125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 description 1
125000005056 dihydrothiazolyl group Chemical group S1C(NC=C1)* 0.000 description 1
UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
238000007598 dipping method Methods 0.000 description 1
150000002016 disaccharides Chemical class 0.000 description 1
231100000676 disease causative agent Toxicity 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000004815 dispersion polymer Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
229960003530 donepezil Drugs 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
238000009506 drug dissolution testing Methods 0.000 description 1
229940126534 drug product Drugs 0.000 description 1
229940088679 drug related substance Drugs 0.000 description 1
239000003596 drug target Substances 0.000 description 1
208000036536 dutch type ABeta amyloidosis Diseases 0.000 description 1
238000004043 dyeing Methods 0.000 description 1
208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
239000003974 emollient agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
206010014599 encephalitis Diseases 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
230000001037 epileptic effect Effects 0.000 description 1
210000000981 epithelium Anatomy 0.000 description 1
229940011871 estrogen Drugs 0.000 description 1
239000000262 estrogen Substances 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
230000003203 everyday effect Effects 0.000 description 1
230000005713 exacerbation Effects 0.000 description 1
230000029142 excretion Effects 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
210000002744 extracellular matrix Anatomy 0.000 description 1
238000000605 extraction Methods 0.000 description 1
229940012952 fibrinogen Drugs 0.000 description 1
102000034240 fibrous proteins Human genes 0.000 description 1
108091005899 fibrous proteins Proteins 0.000 description 1
238000001914 filtration Methods 0.000 description 1
229940014144 folate Drugs 0.000 description 1
OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 1
235000019152 folic acid Nutrition 0.000 description 1
239000011724 folic acid Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
230000037406 food intake Effects 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
230000002538 fungal effect Effects 0.000 description 1
230000000855 fungicidal effect Effects 0.000 description 1
239000000417 fungicide Substances 0.000 description 1
229960003980 galantamine Drugs 0.000 description 1
ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
102000038383 gamma-secretases Human genes 0.000 description 1
108091007739 gamma-secretases Proteins 0.000 description 1
WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
239000000499 gel Substances 0.000 description 1
238000012239 gene modification Methods 0.000 description 1
208000016361 genetic disease Diseases 0.000 description 1
230000005017 genetic modification Effects 0.000 description 1
235000013617 genetically modified food Nutrition 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
230000009229 glucose formation Effects 0.000 description 1
238000007446 glucose tolerance test Methods 0.000 description 1
150000004676 glycans Polymers 0.000 description 1
YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
239000001087 glyceryl triacetate Substances 0.000 description 1
235000013773 glyceryl triacetate Nutrition 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical class COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
201000009277 hairy cell leukemia Diseases 0.000 description 1
230000036541 health Effects 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
230000002440 hepatic effect Effects 0.000 description 1
210000003494 hepatocyte Anatomy 0.000 description 1
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
208000017105 hereditary amyloidosis Diseases 0.000 description 1
125000004475 heteroaralkyl group Chemical group 0.000 description 1
150000002390 heteroarenes Chemical class 0.000 description 1
125000005223 heteroarylcarbonyl group Chemical group 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000003118 histopathologic effect Effects 0.000 description 1
229920002674 hyaluronan Polymers 0.000 description 1
229940099552 hyaluronan Drugs 0.000 description 1
KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
239000008172 hydrogenated vegetable oil Substances 0.000 description 1
150000002433 hydrophilic molecules Chemical class 0.000 description 1
229920001477 hydrophilic polymer Polymers 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
230000001900 immune effect Effects 0.000 description 1
208000026278 immune system disease Diseases 0.000 description 1
238000003018 immunoassay Methods 0.000 description 1
230000005847 immunogenicity Effects 0.000 description 1
102000018358 immunoglobulin Human genes 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
230000003914 insulin secretion Effects 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
229960004903 invert sugar Drugs 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
229920000831 ionic polymer Polymers 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
230000002427 irreversible effect Effects 0.000 description 1
238000002955 isolation Methods 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
239000007951 isotonicity adjuster Substances 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
KXCLCNHUUKTANI-RBIYJLQWSA-N keratan Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@H](COS(O)(=O)=O)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H]([C@@H](COS(O)(=O)=O)O[C@@H](O)[C@@H]3O)O)[C@H](NC(C)=O)[C@H]2O)COS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@@H]1O KXCLCNHUUKTANI-RBIYJLQWSA-N 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
239000004816 latex Substances 0.000 description 1
229920000126 latex Polymers 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000006210 lotion Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
210000003712 lysosome Anatomy 0.000 description 1
230000001868 lysosomic effect Effects 0.000 description 1
239000004325 lysozyme Substances 0.000 description 1
235000010335 lysozyme Nutrition 0.000 description 1
229960000274 lysozyme Drugs 0.000 description 1
201000000564 macroglobulinemia Diseases 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
239000000347 magnesium hydroxide Substances 0.000 description 1
229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
239000000391 magnesium silicate Substances 0.000 description 1
235000019792 magnesium silicate Nutrition 0.000 description 1
229910052919 magnesium silicate Inorganic materials 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
229940035034 maltodextrin Drugs 0.000 description 1
210000001161 mammalian embryo Anatomy 0.000 description 1
150000008146 mannosides Chemical class 0.000 description 1
239000003550 marker Substances 0.000 description 1
235000012054 meals Nutrition 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
229960004640 memantine Drugs 0.000 description 1
230000004630 mental health Effects 0.000 description 1
230000037353 metabolic pathway Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
125000005397 methacrylic acid ester group Chemical group 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
150000002741 methionine derivatives Chemical class 0.000 description 1
239000004530 micro-emulsion Substances 0.000 description 1
244000005700 microbiome Species 0.000 description 1
210000003632 microfilament Anatomy 0.000 description 1
230000006724 microglial activation Effects 0.000 description 1
239000004005 microsphere Substances 0.000 description 1
210000004688 microtubule Anatomy 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000006082 mold release agent Substances 0.000 description 1
239000007932 molded tablet Substances 0.000 description 1
CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
239000000178 monomer Substances 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
210000004897 n-terminal region Anatomy 0.000 description 1
UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
229960002009 naproxen Drugs 0.000 description 1
230000017074 necrotic cell death Effects 0.000 description 1
230000001613 neoplastic effect Effects 0.000 description 1
210000001640 nerve ending Anatomy 0.000 description 1
210000004126 nerve fiber Anatomy 0.000 description 1
230000036403 neuro physiology Effects 0.000 description 1
230000000926 neurological effect Effects 0.000 description 1
231100000189 neurotoxic Toxicity 0.000 description 1
230000002887 neurotoxic effect Effects 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229940060184 oil ingredients Drugs 0.000 description 1
230000004768 organ dysfunction Effects 0.000 description 1
210000004789 organ system Anatomy 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
235000020636 oyster Nutrition 0.000 description 1
238000004806 packaging method and process Methods 0.000 description 1
230000004203 pancreatic function Effects 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
210000004738 parenchymal cell Anatomy 0.000 description 1
235000014594 pastries Nutrition 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
235000020232 peanut Nutrition 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000000813 peptide hormone Substances 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
238000012831 peritoneal equilibrium test Methods 0.000 description 1
230000002688 persistence Effects 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
210000001539 phagocyte Anatomy 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
239000008063 pharmaceutical solvent Substances 0.000 description 1
238000011422 pharmacological therapy Methods 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
230000010399 physical interaction Effects 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
230000007505 plaque formation Effects 0.000 description 1
210000004180 plasmocyte Anatomy 0.000 description 1
229920000058 polyacrylate Polymers 0.000 description 1
229920002647 polyamide Polymers 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
229920001282 polysaccharide Polymers 0.000 description 1
239000005017 polysaccharide Substances 0.000 description 1
239000011118 polyvinyl acetate Substances 0.000 description 1
229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
239000001253 polyvinylpolypyrrolidone Substances 0.000 description 1
235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
238000012636 positron electron tomography Methods 0.000 description 1
238000012877 positron emission topography Methods 0.000 description 1
230000001323 posttranslational effect Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
238000004321 preservation Methods 0.000 description 1
229940097325 prolactin Drugs 0.000 description 1
108060006613 prolamin Proteins 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
239000000473 propyl gallate Substances 0.000 description 1
235000010388 propyl gallate Nutrition 0.000 description 1
229940075579 propyl gallate Drugs 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
239000011253 protective coating Substances 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
230000004845 protein aggregation Effects 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
201000001474 proteinuria Diseases 0.000 description 1
230000017854 proteolysis Effects 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
230000001185 psoriatic effect Effects 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
150000004040 pyrrolidinones Chemical class 0.000 description 1
150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
208000002574 reactive arthritis Diseases 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
201000010174 renal carcinoma Diseases 0.000 description 1
210000003660 reticulum Anatomy 0.000 description 1
238000012552 review Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
229960004136 rivastigmine Drugs 0.000 description 1
238000005070 sampling Methods 0.000 description 1
230000002000 scavenging effect Effects 0.000 description 1
238000007423 screening assay Methods 0.000 description 1
238000007789 sealing Methods 0.000 description 1
230000000580 secretagogue effect Effects 0.000 description 1
230000028327 secretion Effects 0.000 description 1
210000001625 seminal vesicle Anatomy 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
238000002603 single-photon emission computed tomography Methods 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
SRRKNRDXURUMPP-UHFFFAOYSA-N sodium disulfide Chemical compound [Na+].[Na+].[S-][S-] SRRKNRDXURUMPP-UHFFFAOYSA-N 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
CPCPXZQVVRATNS-UHFFFAOYSA-M sodium;1-aminopropane-1-sulfonate Chemical compound [Na+].CCC(N)S([O-])(=O)=O CPCPXZQVVRATNS-UHFFFAOYSA-M 0.000 description 1
KMGJRCNLDZGSFX-UHFFFAOYSA-M sodium;3-aminopropane-1-sulfonate Chemical compound [Na+].NCCCS([O-])(=O)=O KMGJRCNLDZGSFX-UHFFFAOYSA-M 0.000 description 1
239000008279 sol Substances 0.000 description 1
230000003381 solubilizing effect Effects 0.000 description 1
239000012453 solvate Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000010186 staining Methods 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
125000000542 sulfonic acid group Chemical group 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
235000020238 sunflower seed Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
108010033090 surfactant protein A receptor Proteins 0.000 description 1
239000007939 sustained release tablet Substances 0.000 description 1
230000035900 sweating Effects 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
229960001685 tacrine Drugs 0.000 description 1
YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
230000008685 targeting Effects 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000004001 thioalkyl group Chemical group 0.000 description 1
125000000034 thioazolyl group Chemical group 0.000 description 1
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
208000013818 thyroid gland medullary carcinoma Diseases 0.000 description 1
229940036555 thyroid hormone Drugs 0.000 description 1
239000005495 thyroid hormone Substances 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
235000010215 titanium dioxide Nutrition 0.000 description 1
AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
229960000984 tocofersolan Drugs 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
238000011830 transgenic mouse model Methods 0.000 description 1
230000007704 transition Effects 0.000 description 1
238000013519 translation Methods 0.000 description 1
229960002622 triacetin Drugs 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 description 1
238000010977 unit operation Methods 0.000 description 1
201000010653 vesiculitis Diseases 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
210000001835 viscera Anatomy 0.000 description 1
230000004393 visual impairment Effects 0.000 description 1
235000019155 vitamin A Nutrition 0.000 description 1
239000011719 vitamin A Substances 0.000 description 1
235000019165 vitamin E Nutrition 0.000 description 1
229940046009 vitamin E Drugs 0.000 description 1
239000011709 vitamin E Substances 0.000 description 1
229940045997 vitamin a Drugs 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
239000003643 water by type Substances 0.000 description 1
229920003169 water-soluble polymer Polymers 0.000 description 1
239000005019 zein Substances 0.000 description 1
229940093612 zein Drugs 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
239000002076 α-tocopherol Substances 0.000 description 1
235000004835 α-tocopherol Nutrition 0.000 description 1